The Univeristy of Melbourne The Royal Melbourne Hopspital

A joint venture between The University of Melbourne and The Royal Melbourne Hospital

EDUCATION

Research Projects

Project: Beyond integration: defining factors that control HIV latency reversal in both clonal and non-clonal populations

Lewin group

In people living with HIV on combination antiretroviral therapy (ART), life expectancy dramatically improves but the virus persists indefinitely and treatment must continue lifelong. This is due to the presence of silently or ‘latently’ infected cells, which harbour HIV that is not active. One strategy to eliminate these long-lived latently infected cells is to turn on the virus inside the cell. It has been speculated that one major driving force to how a latent virus can turn off or on is the viral integration site, which is where the virus resides inside the host genome. We have recently examined a cell line that contains a single copy of virus integrated in a specific genome. Surprisingly, when we activated the latent virus with a variety of drugs called latency reversing agents, only a subset of the cells responded. This suggests that the response of the latent virus is not solely driven by the site of integration.

In this project, we aim to determine other viral or cellular factors that control the level of virus reactivation. We will use a panel of latently infected cells that each have different integration sites and progressively enrich for cells that do and don’t respond to a specific stimulus. We will then investigate the differences in viral transcription as well as cellular activation, proliferation and transcription in infected cells that do and don’t reactivate virus. During this project, the student will learn and apply a range of laboratory techniques including PC2 and PC3 cell culture, flow cytometry, RNAseq, and real time PCR.

Contact project supervisor for further
information and application enquiries

Project Supervisor

Professor Sharon Lewin

Project Co-supervisor

Dr Jennifer Zerbato

Project availability
PhD/MPhil

Lewin group

[email protected]

1 vacancies

Themes
Immunology
Viral Infectious Diseases
Cross Cutting Disciplines
Translational and Clinical Research

Co-infections with viral or bacterial pathogens cause significant morbidity in people with HIV. In the case of HIV and hepatitis B virus (HBV) co-infection, morbidity and mortality secondary to liver disease is greatly increased compared to those infected with HBV or HIV alone. Mortality remains elevated even after treating both HIV and HBV. The HBV Immunology group investigates the mechanism of how HIV can accelerate liver disease in patients co-infected with HBV. We hypothesise that this occurs by combined effects of HIV and HBV on inflammation in the liver. These studies could potentially lead to new treatments for liver disease.